Compositions for the treatment of pilosebaceous gland inflammations comprising aluminum fluoride

ABSTRACT

The present invention relates to compositions for the treatment of pilosebaceous gland inflammations, especially of the hair follicle and its appendages, in particular of Acne Vulgaris and Folliculitis, comprising as active ingredient AIF or chemical compounds which finally release AIF, or combinations of aluminum and fluoride salts which finally release AIF. AIF in accordance with the present invention relates to Aluminum fluoride (Aluminum Trifluoride; Aluminum Fluoride), CAS No 7784-18-1, EINECS No. 232-051-1, having an empirical formula of AIF 3 . Said compositions have, inter alia, pharmaceutical, cosmetic or quasi-cosmetic properties. The present invention also relates to the use of said compositions in said treatment, and to methods for the treatment of pilosebaceous gland inflammations with said compositions.

This application is a 371 of PCT/lL02/00800, filed on 2 Oct. 2002.

The present invention relates to compositions for the treatment ofpilosebaceous gland inflammations, especially of the hair follicle andits appendages, in particular of Acne Vulgaris and Folliculitis. Saidcompositions have, inter alia, pharmaceutical, cosmetic orquasi-cosmetic properties. The present invention also relates to the useof said compositions in said treatment; and to methods for the treatmentof pilosebaceous gland inflammations with said compositions.

The present invention will be illustrated herein in particular withreference to Acne Vulgaris and Folliculitis but is not restricted tothese pilosebaceous gland inflammations.

The pathophysiology of Acne Vulgaris is multifactorial. It involves agenetic tendency of the hair infundibulum to narrow resulting in akeratin plug formation in the sebaceous gland ductuli. This isaccompanied, in part of the subjects, by an androgenic-related sebumhypersecretion, causing noninflammatory lesions, i.e. closed and opencomedos. Concomitantly, some of the lesions evolve into an inflammatoryprocess, triggered in part by free fatty acids release into the dermis,together with a secondary microbial colonization of the pilosebaceousunit. The overall inflammatory and noninflammatory lesions are definedas Acne Vulgaris. The inflammatory lesions are responsible for the longlasting cosmetically disfiguring scars.

It has been amply described in the past (Fitzpatrick et al., Dermatologyin Internal Medicine, McGraw Hill, In, 4th Edition, 1993) that AcneVulgaris might be exacerbated by exposure to or intake of variouschemicals and molecules, such as mechanical pressure, foods, drugs,halogens, tars, cosmetics and aluminum fluoride-containing toothpastes(Epstein E. Arch. Dermatol Fluoride toothpastes as a cause of acne-likeeruptions, 1976 July, 112(7):10334). An inflammatory process isresponsible for the classical clinical signs, such as papules (elevatedpalpable red areas) and pustules.

A process similar to inflammatory acne is Folliculitis, an “inflammationof a follicle or follicles.” (Dorland's Illustrated Medical Dictionary,WB Saunders Comp., 27th Edition, 1988). It results from a microbialcolonization and infection of the hair follicle shaft. Folliculitis iscommonly accompanied by a perifollicular inflammation, perceived asclassical inflammation signs of redness, swelling and tenderness at thebasis of the hair shaft. More severe cases appear as significantperifollicular inflammation, named furuncle, carbuncles, impetigo, etc.The clinical picture of an inflammatory acne lesion and Folliculitis areidentical, and Folliculitis is part of the acne pathophysiology.Mechanical trauma may induce or aggravate Folliculitis as well. However,a basic difference delineates these two entities: 1) The areas ofdistribution of the lesions in acne are seborrheic (e.g. face, chest,upper back), unlike Folliculitis, which manifests itself on seborrheicand non-seborrheic body areas and 2) Folliculitis is not related togenetic predisposition and hormonal changes.

From a practical point of view the treatment is alike:anti-inflammatories in conjunction with anti-microbials are started inmild cases as topicals. A more severe spread or degree of lesionsrequire a combined systemic treatment. Agents which change thepilosebaceous unit function, such as retinoids, are sometimes used inAcne Vulgaris and stubborn Folliculitis (barbae). Control of AcneVulgaris, specifically, requires the additional use of classical drugs,such as astringents, sulfur and benzoyl peroxide.

As will be detailed below, current treatment of Acne Vulgaris andFolliculitis is either largely ineffective or involves chronic systemicadministration of drugs that cause numerous undesirable side-effects.Hence, it has been desired in the art to provide an effective andconvincing treatment for both entities. A definitive highly efficacious,fast acting and low side effects solution is lacking. Variouscompositions are known in the art for controlling these pilosebaceousrelated disorders and due to lack of efficacy of single compoundsphysicians are compelled to use combined treatments (Krowchuk DP.Treating Acne—A practical guide. Medical Clinics of North America,2000;84) from the list mentioned beneath.

Some of the ingredients useful in said treatments are categorizedhereinafter by their postulated mode of action. However, it is to beunderstood that in some instances these ingredients operate via morethan one mode of action.

Therefore, the following classifications are made herein for the sake ofconvenience only and are given by way of example and do not limit theingredients to the particular application or applications indicated:

-   -   a. Topical antimicrobials such as clindamycin, tetracycline,        erythromycin—having low efficacy;    -   b. Antimicrobials systemic class such as minocycline,        clindamycin, cephalosporin, sulfur-trimethoprim—causing drug        rashes and antibiotic resistance;    -   c. Antimicrobial and radical free generating benzoyl peroxide        having low efficacy;    -   d. Mild steroids (in severe cases applied by way of        intralesional injection)—suitable for short term treatment only,        but aggravating Acne on prolonged use;    -   e. Classical undefined topicals such as sulfur, zinc, resorcin,        salicylic acid—having low efficacy;    -   f. Astringents such as aluminum chloride, resorcin—inefficient        and causing pruritus;    -   g. Topical retinoids such as natural and/or synthetic analogs of        Vitamin A or retinol-like compounds which possess the biological        activity of Vitamin A in the skin as well as the geometric        isomers and stereoisomers of these compounds—causing        photosensitivity, are slow acting and irritating;    -   h. Systemic (isotretinoin) retinoids—drugs with high cost,        relatively high efficacy, having numerous side effects such as        100% dryness, 90% photosensitivity, 30% hair loss, 15%        musculo-skeletal pains, 5% liver function disorder, and lately        reported depression induction and teratogenicity;    -   i. Contraceptives—having all known side effects, from        hyperlipidemia to pulmonary emboli, and are slow acting (require        months of use);    -   j. Others: azelaic acid—having low efficacy; and    -   k. Plant extracts—scientifically non-defined as active.

A mild clinical case of Acne Vulgaris or Folliculitis is usually treatedat the start by two different topicals, such as an anti-microbial andbenzoyl peroxide. Mild steroids might be added. A subject suffering froma moderate condition may need the addition of a systemic antibiotic,with its obvious side effects. Topical retinoids may be addedalternatively. Severe causes are generally treated by the oralisotretinoin. Due to the reluctance of the disease and topatients—derived pressures, some of the physicians are compelled toprescribe high side effect oral isotretinoin (35% incidence of severeside effects; Strauss J S et al, J Am Acad Dermatol, 2001; 45:196-207)even in patients sufferring from a mild Acne Vulgaris.

There thus remains a need to provide improved topical compositions fortreating inflammatory pilosebaceous disorders. There is a particularneed to provide compositions and methods useful against lesions of AcneVulgaris and of Folliculitis which:

-   -   (i) Improve rapidly the pilosebaceous inflammation;    -   (ii) Can be used topically or systemically;    -   (iii) Are available to women without causing teratogenicity; and    -   (iv) Are devoid of oral antibiotic or retinoid side effects.

Aluminum fluoride (Aluminum Trifluoride; Aluminum Fluoride), CAS No7784-18-1, EINECS No. 232-051-1, having an empirical formula of AIF₃,(hereinafter called “AIF”) is an inorganic salt approved for use as anoral care agent, i.e. as “a cosmetic ingredient and excipient used inproducts to polish teeth, act as oral deodorant or provide othercosmetic effects.” (International Cosmetic Ingredient Dictionary andHandbook, Wenninger et al., The Cosmetic, Toiletry and FragranceAssociation 8th Edition, 2000). In addition said compound is used inceramics, as flux in metallurgy; in aluminum manufacture, as inhibitorof fermentation; and as a catalyst in organic reactions.(Merck Index,1996)

It has now surprisingly been found that aluminum fluoride (AIF), orchemical compounds which finally release AIF, or combinations ofaluminum and fluoride salts which finally release AIF, which are appliedas a topical component on inflammatory lesions of Acne Vulgaris andFolliculitis causes an improvement of the lesions. A search of theliterature did not reveal any reference to AIF activity on sebocytes orto a therapeutic effect of AIF on pilosebaceous inflammation, but on thecontrary to adverse effects induced, for example, by fluoridetoothpastes which induce Acne Vulgaris (Arch. Dermatol. Saunders M A,1975, 111:793).

It is the object of the present invention to provide compositions,mostly topical, for controlling inflammation of the pilosebaceous gland.It is a further object of this invention to provide methods forcontrolling inflammation of the pilosebaceous gland.

Because of the ability of AIF to control inflammation of thepilosebaceous gland, said compositions it should be able to be used intreating in addition to Acne Vulgaris and to Folliculitis, related skindisorders in mammalian skin and scalp, such as acne rosacea, seborrhea,impetigo or psoriasis.

The present invention thus consists in compositions for the treatment ofpilosebaceous gland inflammations, comprising as active ingredient AIF(as herein defined) or chemical compounds which finally release AIF, orcombinations of aluminum and fluoride salts which finally release AIF.

The composition according to the present invention suitably comprisesAIF at a concentration from 0.0001-50.0%, preferably between 0.001-5%;advantageously between 0.05-1.0% by weight.

The pilosebaceous gland inflammations to be treated by the compositionaccording the present invention are preferably Acne Vulgaris andFolliculitis.

The composition according to the present invention may comprise alsoadditional pharmaceutically and/or cosmetically acceptable compoundsand/or compositions. It is thus to be understood that all the additionalcompounds and/or compositions mentioned below have to be acceptable.

The active agents may be formulated into various pharmaceutically and/orcosmetically compositions, e.g. a solution, a lotion, a tonic, ashampoo, a gel, a mousse, a wax, a stick, a mask, a soap, a moisturizer,a powder, a perfume, a dye, a brilliantine an aerosol, a pomade, acream, an ointment, a paste, a systemic capsule or tablet.

The composition according to the present invention may be topicallyapplied as such or internally ingested within a suitable carrier,solvent, dissolvent, emulgent, extract, solutions e.g. aqueous,alcoholic, oily, suspension; microemulsion, microcapsules, vesicles,etc.

The composition according to the present invention may also beformulated as an internally ingested tablet, capsule, drops orsuspension. These compositions may comprise several types of carriersincluding, but not limited thereto, solutions, aerosols, emulsions,gels, solids, and liposomes.

The compositions according to the present invention in particular thoseused for the treatment of Acne Vulgaris and of Folliculitis may thusfurther comprise, for example, one or more supplementarypharmaceutically and/or cosmetically active compounds capable offunctioning in different ways to enhance the activity of AIF and/or toprovide other antiacne or antifoliculitis advantages, as follows.

-   -   a. Topical antibiotics, e.g. clindamycin, tetracycline,        erythromycin, sulfacetamide, etc.;    -   b. Antibiotics administered systemically, e.g. tetracycline,        minocycline, doxylin, erythromycin, clindamycin, cephalosporin,        sulfur-trimethoprim, etc.;    -   c. Benzoyl peroxide;    -   d. Topical retinoids, e.g. tretinoic acid, adapalene,        isotretinoin, etc.;    -   e. Systemic retinoids, e.g. isotretinoin, etc;    -   f. Steroids of all strengths, from mild (e.g. hydrocortisone) to        highly potent (e.g. clobetasol propionate);    -   g. Non Steroidal Anti-Inflammatories, of all classes, e.g.        acetic acid derivatives, oxicams, salicylates, fenemates,        pyrazoles, propionic acid derivatives, etc.;    -   h. Topical eicosanoids, e.g. PGE₂, etc;    -   i. Astringents, e.g. aluminum chloride, camphor, allantoin,        resorcin, etc.;    -   j. Antifungals, e.g. triazoles, metronidazole, alyllamines, etc;    -   k. Estrogens, e.g. Contraceptives, etc;    -   l. Antioxidants, e.g. ascorbic acid and its salts, glutathione,        selenium, etc.;    -   m. Compounds that promote the natural tissue production of        nitric oxide e.g. precursors such as L-arginine, or compounds        that directly or indirectly cause the release of nitric oxide,        e.g. glyceryl tri-nitrate.    -   n. Other supplementary actives in use for acne, e.g.        alpha-Hydroxy acids, (such as glycolic acid and lactic acid),        5-alpha reductase inhibitors, azelaic acid, bisabolol, cetyl        betaine, elemental sulfur or its derivatives, lotio calaminae,        salicylic acid, resorcin, zinc, zinc oxide, etc.;    -   o. Vitamins, e.g. Vitamin A, Vitamin C and its salts, tocopherol        (vitamin E) and other esters of tocopherol, pyridoxine,        panthenol, pantothenic acid, etc.;    -   p. Anti Androgens, e.g. Spironolactone, Ciproterone acetate,        5-alpha reductase inhibitors such as finasteride, etc.;    -   q. Topical Sodium-Proton inhibitors, e.g. Amiloride or its        derivatives, etc;    -   r. Topical Amiodarone;    -   s. Plant extracts known for their therapeutic effect, e.g. aloe        vera, chamomile, candelilla wax, cucumber, forsynthia, ginseng,        grape seed, guggal jojoba, lavender, lemon, manjistha, nettle        root, rosemary, pumpkin seed, polygonum, sage, soy, tea tree        oil, thyme, witch hazel etc.;    -   t. Soaps, e.g. soaps containing triclosan, hexachlorophene, seed        or bran oils, dermatological bars, rinsing and cleaning toners,        mild skin abrasives such as aluminum oxide or polyethylene        microspheres, make-ups, etc.; and    -   u. Amino acids, e.g. arginine, tryptophan, etc.

The composition according to the present invention may be applied alsoas part of a physical therapy, e.g. with ultraviolet, blue lightspectrum or infrared radiation, of cryotherapy, of ultrasound, etc.

The composition according to the present invention may be prepared, forexample, by conventional methods as becomes apparent from the Examplesgiven hereinafter.

The present invention also consists in the use of the compositionaccording to the present invention in the preparation of a remedy forthe treatment of humans and animals of pilosebaceous glandinflammations, in particular of Acne Vulgaris and Folliculitis.

The present invention consists also in a method for the treatment ofhumans and animals against pilosebaceous gland inflammations, inparticular against Acne Vulgaris and Folliculitis with a compositionaccording to the present invention.

The present invention has been described in terms of preferredembodiments, but the skilled artisan will appreciate that variousalterations, substitutions, omissions, and changes may be made withoutdeparting from the scope of the present invention. The amounts of saidcompounds being used may be varied in accordance with the specificrequirements.

The present invention will now be illustrated with reference to thefollowing Examples and to the Figs, annexed hereto without being limitedby them.

In said drawings:

FIGS. 1 a, 1 b and 1 c show a lesion of Acne Vulgaris, wherein

-   -   FIG. 1 a shows a lesion of Acne Vulgaris after 0 hour;    -   FIG. 1 b shows a lesion of Acne Vulgaris after 14 hour;    -   FIG. 1 c shows a lesion of Acne Vulgaris after 26 hour;

FIG. 2 shows an Area of Lesion of Acne Vulgaris;

FIGS. 3 a, 3 b and 3 c show a lesion of Folliculitis, wherein:

-   -   FIG. 3 a shows a lesion of Folliculitis after 0 hour;    -   FIG. 3 b shows a lesion of Folliculitis after 10 hour;    -   FIG. 3 c shows a lesion of Folliculitis after 18 hour;

FIG. 4 shows an Area of Lesion of Folliculitis;

FIGS. 5 a, 5 b, 5 c show subject with Severe Acne, wherein:

-   -   FIG. 5 a shows subject with Severe Acne before treatment;    -   FIG. 5 b shows subject with Severe Acne after 6 weeks from start        of treatment;    -   FIG. 5 c shows subject with Severe Acne 4 months later;

FIGS. 6 a and 6 b show subject with Moderate Acne, wherein:

-   -   FIG. 6 a shows subject with Moderate Acne before treatment;    -   FIG. 6 b shows subject with Moderate Acne after 3 months of        treatment; and

FIGS. 7 a and 7 b show the counting of the number of inflammatory acnelesions, wherein

-   -   FIG. 7 a shows mean number of acne lesions on the face, before        and after treatment.    -   FIG. 7 b shows mean number of acne lesions on the back, before        and after treatment.

EXAMPLE 1

An Acne Vulgaris (FIGS. 1 a, 1 b and 1 c) inflammatory lesion on theright cheek of a 12 yrs old subject was treated by AIF trihydrate at0.5% concentration dissolved in water only. The subject applied each 3-4h the solution as a spray. Pictures were performed in a room withartificial constant light by a Sony Mavica FD95 digital camera at aresolution of 1600×1200 pixels. The figures demonstrate rapid fading ofthe papule at 14 h from start of treatment and its final resolution at26 h.

Area of inflammation was measured by image analysis techniques asfollows:

Pictures (FIGS. 1 a, 1 b and 1 c) were saved as a BMP file and loadedinto Scion Imaging software v. 4.02 (NIH, USA). All three pictures wereconcomitantly analyzed on the same frame. First, pictures in gray scalewere smoothed, manually thresholded, turned into a binary picture andthe results transformed to an outline filter. The area of each outlinedpapule was measured by the software (n=3) and data was further plottedand statistically analyzed by student's t-test in FIG. 2 (Sigmaplot,Jandel, Java). The results (FIG. 2) demonstrate that application of AIFheals the inflamed papule within about 24 h (p<0.01 at 14 h and at 26h). Any artisan in the art will recognize the surprising healing processof the papule within one day.

EXAMPLE 2

A Folliculitis (FIGS. 3 a, 3 b and 3 c) inflammatory lesion on the leftposterior thigh a 43 of a 43 yrs old subject was treated by AIFtrihydrate at 0.5% concentration dissolved in water only. The subjectapplied each 3-4 h the solution as a spray. Pictures were performed in aroom with artificial constant light by a Sony Mavica FD95 digital cameraat a resolution of 1600×1200 pixels. FIGS. 3 a, 3 b and 3 c demonstraterapid fading of the papule at 10 h from start of treatment and its finalresolution at 18 h.

Area of inflammation was measured by image analysis techniques asfollows:

Pictures (FIGS. 3 a, 3 b and 3 c) were saved as a BMP file and loadedinto Scion Imaging software v. 4.02 (NIH, USA). All three pictures wereconcomitantly analyzed on the same frame. First, pictures in gray scalewere smoothed, manually thresholded, turned into a binary picture andthe results transformed to an outline filter. The area of each outlinedpapule was measured by the software (n=3) and data was further plottedand statistically analyzed by student's t-test in FIG. 4 (Sigmaplot,Jandel, Java). The results (FIG. 4) demonstrate that application of AIFheals the inflamed papule within about 18 h (p<0.01 at 10 h and p<0.001at 18 h). Any artisan in the art will recognize the surprising healingprocess of the papule within less than one day.

EXAMPLE 3

ANTI-ACNE CREAM o/w emulsion CTFA/INCI CHEMICAL NAME % w/w PART AGLYCERYL STEARATE Self-Emulsifier 10.00 PROPYLENE GLYCOLDICAPRYLATE\DICAPRATE 8.00 CETEARYL ALCOHOL and SODIUM CETEARYL SULFATE5.00 PART B PROPYLENE GLYCOL 3.00 ALUMINUM FLUORIDE 0.30 PARABENS 0.30PURIFIED WATER (AQUA) 69.30 PART C SULPHUR (COLLOIDAL) 4.00 TOTAL 100.00Manufacturing procedure:

-   -   Heat Part A and Part B, separately, at 70-75 C.°    -   Add Part A on Part B under high stirring    -   Cool to RT (room temperature) under moderate stirring    -   Add the ingredient listed in the Part C    -   Add Part C at 40 C.°

EXAMPLE 4

ANTI-ACNE CREAM w/o emulsion CTFA/INCI CHEMICAL NAME % w/w A. OIL PHASEISOPROPYL STEARATE 5.00 PARAFFIN OIL 15.00 PRESERVATIVE 0.20PEG-22/DODECYL GLYCOL COPOLYMER 3.00 HYDROXYOCTYL HYDROXYSTEARATE 5.00METHOXY PEG-22/DODECYL GLYCOL 3.00 COPOLYMER B. WATER PHASE SORBITOL 70%5.00 ALUMINUM FLUORIDE 0.10 WATER 63.70 TOTAL 100.00Manufacturing Procedure:

-   -   Heat Part A and Part B, separately, at 75-80 C.°    -   Add Part A on Part B under high stirring    -   Cool to RT under moderate stirring

EXAMPLE 5

ANTI-ACNE CLEANSING GEL CTFA/INCI CHEMICAL NAME % w/w SODIUM LAUROYLSARCOSINATE 6.70 PROPYLENE GLYCOL 8.00 QUATERNIUM-15 0.20HYDROXYETHYLCELLULOSE 1.00 ALUMINIUM CHLORIDE HEXAHYDRATE 2.00 ALUMINUMFLUORIDE 0.10 WATER (AQUA) 81.50 PERFUME; COLOUR 0.50 TOTAL 100.00Manufacturing Procedure:

-   -   Add Hydroxyethylcellulose in water under high stirring    -   Add Quaternium-15 and mix to dissolution    -   Add aluminum salts and mix to dissolution    -   Add the surfactant Sodium Lauroyl Sarcosinate    -   Add Propylene glycol, perfume and colour

EXAMPLE 6

ANTI-ACNE LOTION GEL CTFA/INCI CHEMICAL NAME % w/w RESORCINOL 0.50MENTHOL 5.00 BISABOLOL 0.20 DEA-OLETH-3 PHOSPHATE 2.50HYDROXYPROPYLCELLULOSE 2.50 AMPHOTERIC - 1 5.00 ALUMINUM FLUORIDE 0.10ALUMINUM CHLORIDE HEXAHYDRATE 2.00 ETHANOL 96% 40.00 WATER 42.20 TOTAL100.00Manufacturing Procedure:

-   -   Add Hydroxypropylcellulose in water under high stirring    -   Add Amphoteric-1 and mix to dissolution    -   Add aluminum salts and mix to dissolution    -   Add the surfactant DEA-Oleth-3 Phosphate    -   Dissolve in alcohol: Bisabolol, Menthol and Resorcinol and add        to mix

EXAMPLE 7

ANTI-ACNE PEELING LOTION CTFA/INCI CHEMICAL NAME % w/w SALICYLIC ACID4.00 ALCOHOL 96% 17.00 ALUMINUM CHLORIDE HEXAHYDRATE 2.00 ALUMINUMFLUORIDE 0.10 ROSE WATER 76.90 TOTAL 100.00Manufacturing Procedure:

-   -   Add the aluminum salts in Rose Water    -   Add and solve salicylic acid in alcohol    -   Add the alcohol in water

EXAMPLE 8

ANTI-ACNE HYDROPHILIC OINTMENT CTFA/INCI CHEMICAL NAME % w/w A. OilPhase PETROLATUM 10.00 MINERAL OIL 10.00 CETOSTEARYL ALCOHOL 4.00ISOSTEARYL ISOSTEARATE 6.00 B. Aqueous Phase SODIUM LAURYL SULPHATE 1.50PURIFIED WATER (AQUA) 38.90 METHYL GLUCETH-20 10.00 ALUMINUM FLUORIDE0.10 C. ACTIVE INGREDIENTS PROPYLENE GLYCOL 15.00 SULFUR COLLOIDAL 4.00PRESERVATIVE 0.50 TOTAL 100.00Manufacturing Procedure:

-   -   Heat Part A and Part B, separately, at 75-80 C.°    -   Add Part A on Part B under high stirring    -   Cool to RT under moderate stirring    -   At 45 C.° add the mix of Part C

EXAMPLE 9

ANTI-ACNE DAY CREAM CTFA/INCI CHEMICAL NAME % w/w A. OIL PHASE ARACHIDYLand BEHENYL ALCOHOL/ 2.00 ARACHIDYLGLUCOSIDE CETEARYL ALCOHOL andCETEARYL GLUCOSIDE 2.00 PROPYLENE GLYCOL DICAPRYLATE/CAPRATE 8.00 OCTYLISOSTEARATE 6.00 PROPYL PARABEN 0.20 B. AQUEOUS PHASE ALUMINUM FLUORIDE0.30 CALCIUM LACTATE 0.25 PURIFIED WATER (AQUA) 74.05 POLYACRYLAMIDE andC13-14 ISOPARAFFIN 0.70 and LAURETH-7 C. ADDITIONAL COMPONENTSCLINDAMYCIN 0.50 PRESERVATIVE 0.50 PROPYLENE GLYCOL 5.00 FRAGRANCE 0.50TOTAL 100.00Manufacturing Procedure:

-   -   Heat Part A and B, separately to 60-65 C.°    -   Add the Part A to Part B and homogenize vigorously    -   Stir under cooling to RT    -   Mix together the component of Part C    -   Add Part C at 40 C.°

EXAMPLE 10

ANTI-ACNE NIGHT CREAM CTFA/INCI CHEMICAL NAME % w/w A. OIL PHASEARACHIDYL/BEHENYL ALCOHOL and 2.00 ARACHIDYLGLUCOSIDE CETEARYL ALCOHOL2.00 ISOSTEARYL ISOSTEARATE 4.00 ISOPROPYL MYRISTATE 4.00 LANOLINALCOHOL 0.50 STEARETH-2 1.20 DIMETHICONE 1.00 B. AQUEOUS PHASE PURIFIEDWATER (AQUA) 70.80 STEARETH-20 0.30 ALUMINUM CHLORIDE HEXAHYDRATE 2.00ALUMINUM FLUORIDE 0.20 COLLOIDAL SULFUR 4.00 C. ADDITIONAL COMPONENTSPRESERVATIVE 0.50 SALICYLIC ACID 2.00 FRAGRANCE 0.50 PROPYLENE GLYCOL5.00 TOTAL 100.00Manufacturing Procedure:

-   -   Heat Part A and B, separately to 60-65 C.°    -   Add the Part A to Part B and homogenize vigorously    -   Stir under cooling to RT    -   Mix together the component of Part C    -   Add Part C at 40 C.°

EXAMPLE 11

A 22 years old woman with severe cystic acne was treated for 12 weekswith aluminum fluoride cream at 0.20 g % concentration, in a creamcontaining sulfur, resorcinol and clindamycin. In the past, she did notrespond to classical topicals, such as benzoyl peroxide, antimicrobialsand topical retinoids or to systemic antibiotic treatment. The subjectapplied the cream thrice daily for the first 6 weeks and twice dailyafterwards. Results are shown in the enclosed FIGS. 5 a, 5 b and 5 c anddemonstrate gradual and complete disappearance of lesions after 4 monthsof treatment. It is obvious for a skilled artisan in the acne treatmentsthat the results are beyond any improvement a common topical canachieve.

EXAMPLE 12

A 15 yrs old student, with mild acne, and previous antimicrobials andbenzoyl peroxide treatment. The subject was instructed to apply twicedaily a 0.15 g % of an aluminum fluoride cream with sulfur and resorcin.Results are shown in enclosed FIGS. 6 a, and 6 b and demonstrate gradualand complete disappearance of lesions after 3 months of treatment.

EXAMPLE 13

Subjects suffering from mild to severe Acne Vulgaris were treated withan anti acne cream containing aluminum fluoride at 0.5% with sulfur,resorcinol and clindamycin. Most of the patients were previously treatedwith either topical antiobiotics, benzoyl peroxide and/or systemicteracyclines. No other antiacne drugs were used during the treatmentperiod. Each subject applied the cream twice daily for 4-8 weeks.Subjects were photoed before and after treatment with a Sony Mavica FD95digital camera at a resolution of 1600×1200 pixels.

Inflammatory lesions were counted on the face (forehead or cheek, n=14subjects, upper figure) and back (n=6 subjects, lower figure).Comparison between mean number of lesions pre and post treatment areshown in enclosed FIGS. 7 a and 7 b and demonstrate unprecedentedaccelerated disappearance of inflammatory lesions at 4 weeks from startof treatment, already. The mean number of lesions decreased from 8.8 4to 1.6 0.9 on one aspect of the face (p<0.001, paired t test) and from11.8 3.3 to 2.5 1.4 on back (p<0.001, paired t test).

Articles:

-   1. Budavary S, Ed., Merck & CO, The Merck Index, an encyclopedia of    chemicals, drugs and biologicals,. Inc., 12^(th) Edition, 1996.-   2. Epstein E. Arch Dermatol. Fluoride toothpastes as a cause of    acne-like eruptions. 1976 July; 112(7):1033-4-   3. Fitzpatrick T B, Eisen A Z, Wolff K et al, Eds., Dermatology in    internal medicine. Mc-Graw-Hill, In., 4^(th) Edition, 1993.-   4. Krowchuk D P. Treating Acne—A practical guide. Medical Clinics of    North America, 2000;84:811-28.-   5. Saunders M A Arch Dermatol. 1975; 111:793 Fluoride toothpastes: a    cause of acne—like eruptions.-   6. Taylor E J, Ed. Dorland's Illustrated Medical Dictionary, WB    Saunders Comp., 27^(th) Edition, 1988-   7. Strauss J S et al, Safety of a new micronized formulation of    isotretinoin in patients with severe recalcitrant nodular acne. J Am    Acad Dermatol, 2001; 45:196-207.-   8. Wenninger J A, Canterbery R C and McEwen G N, Eds., International    Cosmetic Ingredient Dictionary and Handbook, The Cosmetic, Toiletry    and Fragrance Association, 8^(th) Edition, 2000.

1. A composition for the treatment of acne vulgaris and folliculitis,comprising as an active ingredient aluminum fluoride or combinations ofaluminum and fluoride salts which finally release aluminum fluoride,elemental sulfur and resorcin, and wherein said aluminum fluoride ispresent in a concentration from about 0.001% to about 1% by weight. 2.The composition according to claim 1, further comprising apharmaceutically and/or cosmetically acceptable compound.
 3. Thecomposition according to claim 2, comprising one or morepharmaceutically and/or cosmetically acceptable active compoundsselected from the group consisting of: a. topical antibiotics; b.astringents; c. benzoyl peroxide; d. topical retinoids; e. 5-alphareductase inhibitors, azelaic acid, bisabolol, cetyl betaine, lotioncalaminae, salicylic acid, zinc, zinc oxide; f. steroids; g. nonSteroidal Anti-Inflammatories; h. topical eicosanoids; i. plant extractsknown for their therapeutic effect and selected from the groupconsisting of, aloe vera, chamomile, candelilla wax, cucumber,forsynthia, ginseng, grape seed, guggal jojoba, lavender, lemon,manjistha, nettle root, rosemary, pumpkin seed, polygonum, sage, soy,tea tree, oil thyme, and witch hazel; j. antifungals; k. estrogens; l.antioxidants; m. compounds that promote the natural tissue production ofnitric oxide; n. alpha-Hydroxy acids; o. topical Sodium-Protoninhibitors; p. topical Amiodarone; q. soaps; and r. amino acids.
 4. Thecomposition according to claim 1 wherein said composition is in the formof a solution, a lotion, a tonic, a shampoo, a gel, a mousse, a wax, astick, a mask, a soap, a moisturizer, a powder, a perfume, a dye, abrilliantine an aerosol, a pomade, a cream, an ointment, a paste, asystemic capsule or tablet.
 5. The composition according to claim 1further comprising a pharmaceutical composition.
 6. The compositionaccording to claim 1 further comprising a cosmetic composition.
 7. Thecomposition of claim 1, wherein said aluminum fluoride is present in aconcentration from about 0.15% to about 0.5% by weight.
 8. Thecomposition of claim 1, wherein said aluminum fluoride is present in aconcentration from about 0.2 to about 0.3% by weight.
 9. A method forthe treatment of humans and animals against acne vulgaris andfolliculitis containing administering a composition according toclaim
 1. 10. The method for treating humans and animals against acnevulgaris and folliculitis according to claim 9 further comprisingtreating said human or animal with a physical therapy selected from thegroup consisting of ultraviolet, blue light spectrum, infraredradiation, cryotherapy and ultrasound.
 11. The method according to claim9 wherein said composition is in the form of a solution, a lotion, atonic, a shampoo, a gel, a mousse, a wax, a stick, a mask, a soap, amoisturizer, a powder, a perfume, a dye, a brilliantine an aerosol, apomade, a cream, an ointment, or a paste, and wherein said administeringstep comprises applying said composition topically.
 12. The method ofclaim 9, wherein said aluminum fluoride is present in a concentrationfrom about 0.15% to about 0.5% by weight.
 13. The method of claim 9,wherein said aluminum fluoride is present in a concentration from about0.2 to about 0.3% by weight.